Study to Assess the Effect of Omecamtiv Mecarbil on Exercise Capacity in Subjects With Heart Failure

NCT03759392 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: CY 10312018-001233-40
• Study Type: interventional
• Target: 276
• Locations: 9 countries
• Sites: 81

Brief Summary

The purpose of this study is to evaluate the effect of treatment with omecamtiv mecarbil compared with placebo on exercise capacity as determined by cardiopulmonary exercise testing following 20 weeks of treatment with omecamtiv mecarbil or placebo

Conditions

Heart Failure With Reduced Ejection Fraction

Outcome Measures

Primary Outcomes (1)

• Change in Peak Oxygen Uptake on Cardiopulmonary Exercise Testing From Baseline to Week 20

  The effect of treatment on exercise capacity, as assessed by peak oxygen uptake, was assessed during cardiopulmonary exercise testing (CPET) with gas-exchange analysis. Cycle ergometry was the preferred modality for exercise testing; treadmill exercise testing was an acceptable alternative. Participants were to use the same testing modality for all exercise tests during the study. Whenever possible, CPET was administered by the same study personnel using the same equipment throughout the study.

  Baseline and Week 20

Secondary Outcomes (3)

• Change in Total Workload During Cardiopulmonary Exercise Testing From Baseline to Week 20

  Baseline and Week 20

• Change in Ventilatory Efficiency During Cardiopulmonary Exercise Testing From Baseline to Week 20

  Baseline and Week 20

• Change in the Average Daily Activity Units Measured Over a 2-week Period From Baseline (Week -2 to Day 1) to Weeks 18-20

  Baseline (Week -2 to Day 1) to Weeks 18-20

Study Arms (2)

Omecamtiv Mecarbil

EXPERIMENTAL

Omecamtiv mecarbil was administered as an oral modified-release tablet twice daily for up to 20 weeks. Participants randomized to this arm started at an omecamtiv mecarbil dose of 25 mg twice daily. The dose could be increased based on plasma concentrations at Weeks 2 and 6.

Drug: Omecamtiv Mecarbil

Placebo

PLACEBO COMPARATOR

Participants randomized this arm received placebo tablets (matching the appearance of the omecamtiv mecarbil tablets) twice daily for up to 20 weeks.

Drug: Placebo

Interventions

Omecamtiv Mecarbil DRUG

Oral omecamtiv mecarbil twice daily for up to 20 weeks with dose level determined by periodic blood testing

Also known as: CK-1827452, AMG-423

Omecamtiv Mecarbil

Placebo DRUG

Oral placebo twice daily for up to 20 weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, greater than or equal to 18 to lesser than or equal to 85 years of age
• History of chronic HF, defined as requiring continuous treatment with medications for HF for a minimum of 3 months before screening
• New York Heart Association (NYHA) class II or III at screening
• Left ventricular ejection fraction less than or equal to 35%
• On maximally tolerated HF standard of care (SoC) therapies consistent with regional clinical practice guidelines, if not contraindicated and according to investigator judgment of the subject's clinical status. Beta blocker dose must be stable for 30 days prior to randomization.
• N-terminal (NT)-proBNP level greater than or equal to 200 pg/mL
• Peak VO2 less than or equal to 75% of the predicted normal value with respiratory exchange ratio (RER) greater than or equal to 1.05 on a screening CPET, confirmed by a CPET core laboratory

You may not qualify if:

• Severe uncorrected valvular heart disease
• Paroxysmal atrial fibrillation or flutter documented within the previous 6 months, direct-current (DC) cardioversion or ablation procedure for atrial fibrillation within 6 months, or plan to attempt to restore sinus rhythm within 6 months of randomization. Subjects with persistent atrial fibrillation and no sinus rhythm documented in the prior 6 months are permitted.
• Symptomatic bradycardia, second-degree Mobitz type II, or third-degree heart block without a pacemaker.
• History of gastrointestinal bleeding requiring hospitalization, urgent procedure or transfusion in the prior year, or received intravenous (IV) iron, blood transfusion, or an erythropoiesis-stimulating agent (ESA) within 3 months prior to screening, or planned blood transfusion or ESA use during the study screening or treatment period. Chronic, stable use of oral iron is permitted.
• Ongoing or planned enrollment in cardiac rehabilitation.
• Requires assistance to walk or use of mobility assistive devices such as motorized devices, wheelchairs, or walkers. The use of canes for stability while ambulating is acceptable if the subject is deemed capable of performing CPET.
• Major medical event or procedure within 3 months prior to randomization, including: hospitalization, surgery, renal replacement therapy or cardiac procedure. This includes episodes of decompensated HF that require IV HF treatment.
• At screening: Resting systolic BP greater than 140 mmHg or less than 85 mmHg, or diastolic BP greater than 90 mmHg (mean of triplicate readings); Resting heart rate greater than 90 beats per minute, or less than 50 beats per minute (mean of triplicate readings); Estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73m2 (by the modified Modification of Diet in Renal Disease equation); Hepatic impairment defined by a total bilirubin (TBL) greater than or equal to 2 times the upper limit of normal (ULN), or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 3 times ULN. Patients with documented Gilbert syndrome and TBL greater than or equal to 2 times ULN due to unconjugated hyperbilirubinemia, without other hepatic impairment, are permitted.
• Room air oxygen saturation under 90% at screening
• Hemoglobin less than 10.0 g/dL at screening
• Significant adverse finding (e.g., exercise-induced early ischemic changes, abnormal decrease in BP \[systolic BP falls by more than 10 mmHg\], unexpected arrhythmia or other serious finding) during CPET at screening that precludes safe participation in the study, per investigator
• Chronotropic incompetence (including inadequate pacemaker rate response) during CPET at screening, defined as a maximum heart rate \<60% of the maximum predicted heart rate

Sponsors & Collaborators

• Cytokinetics: lead

Study Sites (81)

Alaska Heart and Vascular Institute

Anchorage, Alaska, 99508, United States

Location

Arkansas Cardiology Clinic

Little Rock, Arkansas, 72205, United States

Location

Harbor-UCLA Medical Center

Torrance, California, 90509, United States

Location

South Denver Cardiology Associates, PC

Littleton, Colorado, 80120, United States

Location

Hartford Hospital-University of Connecticut School of Medicine

Hartford, Connecticut, 06102, United States

Location

Holy Cross Hospital - Fort Lauderdale

Fort Lauderdale, Florida, 33308-4603, United States

Location

Broward Research Center - Pembroke Pines

Pembroke Pines, Florida, 33024, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Community Hospital South, Inc.

Indianapolis, Indiana, 46227, United States

Location

Saint Vincent Medical Group Inc.

Indianapolis, Indiana, 46260, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Massachusetts General Hospital (MGH) - Cardiac Unit Associates

Boston, Massachusetts, 02114-2621, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Heart & Vascular Institute

Detroit, Michigan, 48202, United States

Location

McLaren Health Care Corporation

Petoskey, Michigan, 49770, United States

Location

Michigan Heart

Ypsilanti, Michigan, 48197, United States

Location

Saint Luke's Health System

Kansas City, Missouri, 64111, United States

Location

Glacier View Research Institute, Cardiology

Kalispell, Montana, 59901, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Cardiovascular Associates Of The Delaware Valley (Cadv), P.A. - Elmer Physicians Care Center - Elmer

Elmer, New Jersey, 08318, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

NYU Langone Medical Center

New York, New York, 10016, United States

Location

Queens Heart Institute

Rosedale, New York, 11422, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Med Health and Hospital

Raleigh, North Carolina, 27610, United States

Location

Wake Forest University School of Medicine

Winston-Salem, North Carolina, 27101, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

St. John Clinical Research Institute

Tulsa, Oklahoma, 74104, United States

Location

Oregon Health

Portland, Oregon, 97239, United States

Location

Capital Area Research, LLC

Camp Hill, Pennsylvania, 17011, United States

Location

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, 17033, United States

Location

Lancaster Heart And Stroke Foundation

Lancaster, Pennsylvania, 17603, United States

Location

Greenville Health System

Greenville, South Carolina, 29605, United States

Location

University of Texas - Southwestern Medical Center

Dallas, Texas, 75235, United States

Location

Baylor Scott and White Heart and Vascular Hospital

Dallas, Texas, 75246, United States

Location

Inova Heart and Vascular Institute

Falls Church, Virginia, 22042, United States

Location

Foothills Medical Centre

Calgary, Alberta, T2N 4Z6, Canada

Location

London Health Sciences Centre - University Hospital

London, Ontario, N6A 5A5, Canada

Location

Ecogene-21

Chicoutimi, Quebec, G7H 7K9, Canada

Location

Universite de Montreal Institut de Cardiologie de Montreal ICM Montreal Heart Institute MHI

Montreal, Quebec, H1Y 3N1, Canada

Location

Mcgill University Health Centre (MUHC)-The Montreal General Hospital (MGH)

Montreal, Quebec, H3P1E1, Canada

Location

Centre Hospitalier De La Cote Basque

Bayonne, 64109, France

Location

Groupe Hospitalier Mutualiste de Grenoble

Grenoble, 38028, France

Location

Centre Hospitalier Universitaire de Grenoble-Hopital Albert Michallon

La Tronche, 38700, France

Location

Universite De Nantes - L'Institut Du Thorax

Nantes, 44093, France

Location

Assistance Publique - Hopitaux de Paris (AP-HP) - Hopital Lariboisiere

Paris, 75010, France

Location

Chu de Rouen Hopital Charles Nicolle

Rouen, 76031, France

Location

Centre Hospitalier Universitaire (CHU) de Toulouse - Hopital Rangueil

Toulouse, 31059, France

Location

Universitaetsklinik Heidelberg

Heidelberg, Baden-Wurttemberg, 69120, Germany

Location

Universitatsklinikum Magdeburg

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

Universitaetsklinikum Jena

Jena, Thuringia, 07747, Germany

Location

Kerckhoff-Klinik- Bad Nauheim

Bad Nauheim, 61231, Germany

Location

Praxisklinik Dresden

Dresden, 01099, Germany

Location

Universitaetsklinikum Des Saarlandes Und Medizinische Fakultaet Der Universitaet Des Saarlandes

Homburg, 66421, Germany

Location

Balatonfuredi Allami Szivkorhaz

Balatonfüred, 8230, Hungary

Location

Semmelweis University Heart and Vascular Center

Budapest, 1122, Hungary

Location

Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) (University of Pecs Medical School)

Pécs, 7624, Hungary

Location

Ospedali Riuniti Foggia

Foggia, Apulia, 71100, Italy

Location

Centro Cardiologico Monzino IRCCS

Milan, Lombardy, 20138, Italy

Location

Azienda Ospedaliera S.Orsola Malpighi

Bologna, Province of Bologna, 40138, Italy

Location

Azienda Ospedaliera Spedali Civili di Brescia-Universita degli Studi Di Brescia

Brescia, Province Of Brescia, 25123, Italy

Location

Insituto Di Ricovero E Cura A Carattere Scientifico San Raffaele Pisana

Roma, Rome, 00163, Italy

Location

Divisione di Cardiologia con Utic ed Emodinamica

Napoli, 80131, Italy

Location

Ospedale Monaldi

Napoli, 80131, Italy

Location

Erasmus MC - Universitair Medisch Centrum Rotterdam

Rotterdam, South Holland, 3000 CA, Netherlands

Location

Jeroen Bosch Ziekenhuis

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Onze Lieve Vrouwe Gasthuis (OLVG) Locatie West

Amsterdam, 1061 AE, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Leids Universitair Medisch Centrum (LUMC)

Leiden, 2300RC, Netherlands

Location

Radboud Universiteit - Radboud Universitair Medisch Centrum (Radboudumc)

Nijmegen, 6500 HB, Netherlands

Location

Universitair Medisch Centrum Utrecht - Wilhelmina Kinderziekenhuis

Utrecht, 3584 CX, Netherlands

Location

Maxima Medisch Centrum Veldhoven

Veldhoven, 5504 DB, Netherlands

Location

Centrum Medyczne Medyk Sp z o.o. Sp. k.

Rzeszów, Podkarpackie Voivodeship, 35-055, Poland

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, 15-276, Poland

Location

Uniwersyteckie Centrum Kliniczne Kliniczne Centrum Kardiologii

Gdansk, 80-952, Poland

Location

Oddzial Kliniczny Choroby Wiencowej i Niewydolnosci Serca z Pododdzialem Intensywnego Nadzoru Kardiologicznego

Krakow, 31- 202, Poland

Location

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii im. M. Kopernika, Oddzial Kardiologiczny

Lodz, 93-513, Poland

Location

Instytut Kardiologii Heart Failure Clinic

Warsaw, 04-628, Poland

Location

Centrum Chorob Serca, Uniwersytecki Szpital Kllniczny im. Jana Mikulicza Radeckiego we Wrociawiu

Wroclaw, 50556, Poland

Location

Sahlgrenska Universitetssjukhuset

Gothenburg, 413 45, Sweden

Location

Enhet Klinisk forskning, hjartmedicin, Skanes Universitet Sjukhus

Lund, 22242, Sweden

Location

Related Publications (2)

• Lewis GD, Voors AA, Cohen-Solal A, Metra M, Whellan DJ, Ezekowitz JA, Bohm M, Teerlink JR, Docherty KF, Lopes RD, Divanji PH, Heitner SB, Kupfer S, Malik FI, Meng L, Wohltman A, Felker GM. Effect of Omecamtiv Mecarbil on Exercise Capacity in Chronic Heart Failure With Reduced Ejection Fraction: The METEORIC-HF Randomized Clinical Trial. JAMA. 2022 Jul 19;328(3):259-269. doi: 10.1001/jama.2022.11016.

  PMID: 35852527 DERIVED

• Lewis GD, Docherty KF, Voors AA, Cohen-Solal A, Metra M, Whellan DJ, Ezekowitz JA, Ponikowski P, Bohm M, Teerlink JR, Heitner SB, Kupfer S, Malik FI, Meng L, Felker GM. Developments in Exercise Capacity Assessment in Heart Failure Clinical Trials and the Rationale for the Design of METEORIC-HF. Circ Heart Fail. 2022 May;15(5):e008970. doi: 10.1161/CIRCHEARTFAILURE.121.008970. Epub 2022 Mar 3.

  PMID: 35236099 DERIVED

MeSH Terms

Interventions

omecamtiv mecarbil

Results Point of Contact

• Title: Cytokinetics MD
• Organization: Cytokinetics, Inc.

medicalaffairs@cytokinetics.com

650-624-2929

Study Officials

• Cytokinetics, MD

  Cytokinetics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 15, 2018
• First Posted: November 30, 2018
• Study Start: April 9, 2019
• Primary Completion: November 8, 2021
• Study Completion: January 6, 2022
• Last Updated: March 7, 2023
• Results First Posted: March 7, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.

Locations

DE (6); US (36); FR (7); HU (3); CA (5); NL (8); PL (7); IT (7); SE (2)